A damage-specific DNA binding protein from human cells will be employed as a probe for nucleotide damage in DNA. This protein recognizes lesions in DNA treated with UV light or X-rays, as well as in HNO2-, NaHSO3-, H2O2-or OsO4- treated DNA. The protein does not bind, however, to apurinic sites, single-strand breaks, single-strand regions, thymine dimers or psoralen-induced crosslinks in DNA. Thus, the protein functions as a broad-specificity probe for monofunctional base damage in DNA. In this work, we will further characterize this protein and use it to follow damage introduction into DNA treated with a variety of mutagenic or carcinogenic agents. In addition, a variety of genetic disorders characterized by abnormal sensitivity to radiation will be screened for the presence of this protein.